Impact of detectable monoclonal protein at diagnosis on outcomes in marginal zone lymphoma: A multicenter cohort study

Given the paucity of data surrounding the prognostic relevance of monoclonal paraprotein (M-protein) in marginal zone lymphoma (MZL), we sought to evaluate the impact of detecting M-protein at diagnosis on outcomes in patients with MZL in a large retrospective cohort. The study included 547 patients receiving first-line therapy for MZL. M-protein was detectable at diagnosis in 173 (32%) patients. There was no significant difference in the time from diagnosis to initiation of any therapy (systemic and local) between the M-protein and no M-protein groups. Patients with M-protein at diagnosis had significantly inferior progression-free survival (PFS) compared with those without M-protein at diagnosis. After adjusting for factors associated with inferior PFS in univariate models, presence of M-protein remained significantly associated with inferior PFS (hazard ratio, 1.74; 95% confidence interval, 1.20-2.54; P = .004). We observed no significant difference in the PFS based on the type or quantity of M-protein at diagnosis. There were differential outcomes in PFS based on the first-line therapy in patients with M-protein at diagnosis, in that, those receiving immunochemotherapy had better outcomes compared with those receiving rituximab monotherapy. The cumulative incidence of relapse in stage 1 disease among the recipients of local therapy was higher in the presence of M-protein; however, this did not reach statistical significance. We found that M-protein at diagnosis was associated with a higher risk of histologic transformation. Because the PFS difference related to presence of M-protein was not observed in patients receiving bendamustine and rituximab, immunochemotherapy may be a preferred approach over rituximab monotherapy in this group and needs to be explored further

Impact of early relapse within 24 months after first-line systemic therapy (POD24) on outcomes in patients with marginal zone lymphoma: A US multisite study

Progression of disease within 24 months (POD24) from diagnosis in marginal zone lymphoma (MZL) was shown to portend poor outcomes in prior studies. However, many patients with MZL do not require immediate therapy, and the time from diagnosis-to-treatment interval can be highly variable with no universal criteria to initiate systemic therapy. Hence, we sought to evaluate the prognostic relevance of early relapse or progression within 24 months from systemic therapy initiation in a large US cohort. The primary objective was to evaluate the overall survival (OS) in the two groups. The secondary objective included the evaluation of factors predictive of POD24 and the assessment of cumulative incidence of histologic transformation (HT) in POD24 versus non-POD24 groups. The study included 524 patients with 143 (27%) in POD24 and 381 (73%) in non-POD24 groups. Patients with POD24 had inferior OS compared to those without POD24, regardless of the type of systemic therapy received (rituximab monotherapy or immunochemotherapy) at diagnosis. After adjusting for factors associated with inferior OS in the univariate Cox model, POD24 remained associated with significantly inferior OS (HR = 2.50, 95% CI = 1.53-4.09, p = 0.0003) in multivariable analysis. The presence of monoclonal protein at diagnosis and those who received first-line rituximab monotherapy had higher odds of POD24 on logistic regression analysis. Patients with POD24 had a significantly higher risk for HT compared to those without POD24. POD24 in MZL might be associated with adverse biology and could be used as an additional information point in clinical trials and investigated as a marker for worse prognosis

The feasibility of using sonoelastography to identify the effect of joint hypermobility syndrome on elasticity of gastrocnemius muscle

Background: Joint hypermobility syndrome (JHS) is a heritable connective tissue disorder in which multiple synovial joints demonstrate a painful and extraordinary range of motion. Genetically there are abnormal changes in the connective tissue matrix in people with JHS, and that may alter the viscoelasticity of their muscular tissue. Sonoelastography (SEG) is a new technology in musculoskeletal practice for assessing tissue elasticity. This study aimed to determine the feasibility of using SEG to distinguish between those with and without a diagnosis of JHS. Gastrocnemius muscle (GM) elasticity was examined, as it is essential for balance and walking.Methods: Twenty participants were examined in a cross-sectional feasibility study: 10 participants diagnosed with JHS and 10 age- and gender-matched healthy controls. The dominant GM was scanned three times using SEG. The colours of the SEG images indicate soft (red), intermediate (green) and hard (blue) tissues. ImageJ software was used to analyse the images by identifying the mean percentage of pixels of each colour.Results: For the JHS group, nine females and one male were examined, with a mean age of 38.9 years (S.D. 15.53). Similarly, for the non-JHS group, nine females and one male were examined, with a mean age of 38.9 years (S.D. 12.37). The groups were comparable in terms of age, gender and BMI (P = 1.00, 1.00, and 0.77, respectively).The JHS group had a significantly higher percentage of blue (hard tissue) pixels when compared with the control group (P = 0.035). No significant differences were found in the mean percentage of green (intermediate) and red (soft) pixels (P = 0.55 and P = 0.051, respectively).SEG required a reasonable amount of training for clinicians with sufficient background in musculoskeletal anatomy, 4 h of observation and practical training. The examination was completed in < 5 min, so it may be reasonable for use in clinical practice, and it was well tolerated by patients. The SEG image was analysed in < 5 minutes.Conclusion: The results indicate that the GM in people with JHS had more areas of hard tissue when compared with the control group, contradicting the expected results. However, GM hyperactivity has been identified during walking in people with JHS, and increased muscle tone might therefore explain the findings. The findings need to be verified in a much larger future study. The SEG seems a feasible tool for quantifying muscular tissue elasticity in JHS

Birth room transition support for term and near-term infants : A cochrane overview

This is a protocol for a Cochrane Review (Overview). The objectives are as follows: We will describe and summarise Cochrane Reviews of birth room interventions for term or near-term newborn infants, and assess their methodological quality and the validity of their findings. We will map the evidence from Cochrane Reviews and identify important gaps in the evidence base. We will not compare multiple interventions with the intention of drawing inferences about their comparative effectiveness

Birth room transition support for preterm infants : A cochrane overview

This is a protocol for a Cochrane Review (Overview). The objectives are as follows: We will describe and summarise Cochrane Reviews of birth room interventions for preterm infants, and assess their methodological quality and the validity of their findings.We will map the evidence from Cochrane Reviews and identify important gaps in the evidence base. We will not compare multiple interventions with the intention of drawing inferences about their comparative effectiveness

Validation of Multisource Feedback in Assessing Medical Performance: A Systematic Review

Introduction Over the past ten years, a number of systematic reviews have evaluated the validity of multisource feedback (MSF) to assess and quality assure medical practice. The purpose of this study is to synthesise the results from existing reviews to provide a holistic overview of the validity evidence. Methods This review identified eight systematic reviews evaluating the validity of MSF published between January 2006 and October 2016. Using a standardised data extraction form, two independent reviewers extracted study characteristics. A framework of validation developed by the American Psychological Association (APA) was used to appraise the validity evidence within each systematic review. Results In terms of validity evidence, each of the eight reviews demonstrated evidence across at least one domain of the APA validity framework. Evidence of assessment validity within the domains of ‘internal structure’ and ‘relationship to other variables’ has been well established. However, the domains of content validity (i.e. ensuring MSF tools measure what they are intended to measure); consequential validity (i.e. evidence of the intended or unintended consequences MSF assessments may have on participants or wider society) and response process validity (i.e. the process of standardisation and quality control in the delivery and completion of assessments) remain limited. Discussion Evidence for the validity of MSF has, across a number of domains, been well-established. However, the size and quality of the existing evidence remains variable. In order to determine the extent to which MSF is considered a valid instrument to assess medical performance, future research is required to determine: 1) how best to design and deliver MSF assessments that address the identified limitations of existing tools, and 2) how to ensure involvement within MSF supports positive changes in practice. Such research is integral if MSF is to continue to inform medical performance and subsequent improvements in the quality and safety of patient care

Development of a biomimetic collagen-hydroxyapatite scaffold for bone tissue engineering using a SBF immersion technique.

The objective of this study was to develop a biomimetic, highly porous collagen-hydroxyapatite (HA) composite scaffold for bone tissue engineering (TE), combining the biological performance and the high porosity of a collagen scaffold with the high mechanical stiffness of a HA scaffold. Pure collagen scaffolds were produced using a lyophilization process and immersed in simulated body fluid (SBF) to provide a biomimetic coating. Pure collagen scaffolds served as a control. The mechanical, material, and structural properties of the scaffolds were analyzed and the biological performance of the scaffolds was evaluated by monitoring the cellular metabolic activity and cell number at 1, 2, and 7 days post seeding. The SBF-treated scaffolds exhibited a significantly increased stiffness compared to the pure collagen group (4-fold increase), while a highly interconnected structure (95%) was retained. FTIR indicated that the SBF coating exhibited similar characteristics to pure HA. Micro-CT showed a homogeneous distribution of HA. Scanning electron microscopy also indicated a mineralization of the collagen combined with a precipitation of HA onto the collagen. The excellent biological performance of the collagen scaffolds was maintained in the collagen-HA scaffolds as demonstrated from cellular metabolic activity and total cell number. This investigation has successfully developed a biomimetic collagen-HA composite scaffold. An increase in the mechanical properties combined with an excellent biological performance in vitro was observed, indicating the high potential of the scaffold for bone TE

Employing Plant Functional Groups to Advance Seed Dispersal Ecology and Conservation

Seed dispersal enables plants to reach hospitable germination sites and escape natural enemies. Understanding when and how much seed dispersal matters to plant fitness is critical for understanding plant population and community dynamics. At the same time, the complexity of factors that determine if a seed will be successfully dispersed and subsequently develop into a reproductive plant is daunting. Quantifying all factors that may influence seed dispersal effectiveness for any potential seed-vector relationship would require an unrealistically large amount of time, materials and financial resources. On the other hand, being able to make dispersal predictions is critical for predicting whether single species and entire ecosystems will be resilient to global change. Building on current frameworks, we here posit that seed dispersal ecology should adopt plant functional groups as analytical units to reduce this complexity to manageable levels. Functional groups can be used to distinguish, for their constituent species, whether it matters (i) if seeds are dispersed, (ii) into what context they are dispersed and (iii) what vectors disperse them. To avoid overgeneralization, we propose that the utility of these functional groups may be assessed by generating predictions based on the groups and then testing those predictions against species-specific data. We suggest that data collection and analysis can then be guided by robust functional group definitions. Generalizing across similar species in this way could help us to better understand the population and community dynamics of plants and tackle the complexity of seed dispersal as well as its disruption

Roles of Hormone Replacement Therapy and Menopause on Osteoarthritis and Cardiovascular Disease Outcomes: A Narrative Review

Osteoarthritis (OA) is a highly prevalent condition characterized by degradation of the joints. OA and cardiovascular disease (CVD) are leading contributors to disease burden worldwide, with a high level of overlap between the risk factors and occurrence of both conditions. Chief among the risk factors that contribute to OA and CVD are sex and age, which are both independent and interacting traits. Specifically, the prevalence of both conditions is higher in older women, which may be mediated by the occurrence of menopause. Menopause represents a significant transition in a women's life, and the rapid decline in circulating sex hormones, estrogen and progesterone, leads to complex physiological changes. Declines in hormone levels may partially explain the increase in prevalence of OA and CVD in post-menopausal women. In theory, the use of hormone therapy (HT) may buffer adverse effects of menopause; however, it is unclear whether HT offers protective effects for the onset or progression of these diseases. Studies have shown mixed results when describing the influence of HT on disease risk among post-menopausal women, which warrants further exploration. The roles that increasing age, female sex, HT, and CVD play in OA risk demonstrate that OA is a multifaceted condition. This review provides a timely consolidation of current literature and suggests aims for future research directions to bridge gaps in the understanding of how OA, CVD, and HT interact in post-menopausal women